IL-12协同B7-1增强实验小鼠的抗肿瘤免疫

IL-12 Synergizes B7-1 Enhance the Antitumor Immunity in Experimental Mice

目的：我们应用逆转录病毒构建了ＩＬ－１２，Ｒ７－１和ＧＭ－ＣＳＦ表达载体，以研究基因修饰的肿瘤细胞的癌疫苗作用。方法：将３种表达载体分别转染ＥＭ胸腺瘤细胞并研究了该基因导入细胞的抗肿瘤免疫效果。结果：当接种了ＥＬ－４／ＩＬ－１２细胞后，在Ｃ５７ＢＬ／６同系鼠中其基因导入细胞的肿瘤原性比较ＥＬ－４和ＥＬ－４／Ｎｅｏ组明显减少（Ｐ＜０．０１）。在ＥＬ－４／ＩＬ－１２被排斥后，体内试验中诱发了实验动物抗 ＥＬ－４／Ｗｔ的系统性、保护性免疫，５１Ｃｒ释放测定中，获得一个较强的抗ＥＬ－４／Ｗｔ和一个较弱的抗同系Ｌｅｗｉｓ肿瘤细胞的ＣＴＬ活性，体内淋巴细胞消除分析的结果提示减少的肿瘤原性主要依赖于ＣＤ４＋，ＣＤ８＋和ＮＫ细胞。用ＥＬ－４／ＩＬ－１２细胞进行疫苗治疗比较用ＥＬ－４／Ｎｅｏ细胞能有效地延缓已建立的ＥＬ－４／Ｗｔ肿瘤的生长（Ｐ＜０．００５），ＥＬ－４／ＩＬ－１２和ＥＬ－４／Ｂ７－１联合比用单一的转基因细胞增强了治疗效果（Ｐ＜０．００５）。结论：提示应用ＩＬ－１２进行血液肿瘤的治疗是有效的，ＩＬ－１２和Ｂ７－１联合使用在未来人类癌症的治疗中亦可有一定的应用前景。

Objective: To study the vaccine potency of gene-modified tumor cells, we have constructed IL-12, H7-1 and GM-CSF express vector using retrovirus. Methods: It was transfected into EL-4 thymic lylmphoma cells respectively and the effect of gene transduction on anti-tumor immunity were investigated. Results: The tumorigenicity of EL-4/IL-12 transfectant in C57BI/6 syn- ergistical mice was decreased significantly after implanted with EL-4/IL-12 transfectant compaired with EL-4/Wt or EL-4/Neo groups (P<0. 01). The systemic protective immunity was induced against the challenge with EL-4/Wt (in 10/15 mice) after the rejection of EL-4/IL-12 in the experiment, a stronger CTL activity against EL-4/Wt cells and a weak killer activity against syn- geneic Lewis Lung Carcinoma cells were obtained in 51Cr release assay. In vivo depletion analysis suggested that the decreased tumorigenicity mainly depended on CD4+, CD8+ and NK cells. Therapeutic vaccines with EL-4/IL-12 cells could retard the growth to estabished EL-4/Wt tumors significantly compared with those of EL-4/Neo(P < 0 .005 ), combination of therapeutic vaccines of EL-4/IL-12 and EL-4/B7-1 result in the enhanced the therapeutic effect of each single transficants (P < 0 .005) in this experimental model. Conclution: These studies suggested that immunogene treatment using IL-12 is effective in hematopoi- etic malignancy, and combination of IL-12 with B7-1 have a aplication value in human cancer treatment in the near future.